PIR-B negatively regulates IL-13-induced esophageal eosinophil effector functions. Mus musculus

Eosinophilic esophagitis (EoE) is a T helper type 2 (TH2) cytokine-associated disease charaterized by eosinophil infiltration, epithelial cell hyperplasia and tissue remodeling. Recent studies have highlighted a major contribution for IL-13 in EoE pathogenesis. Paired immunoglobulin-like receptor (PIR)-B is a cell surface immune-inhibitory receptor that is expressed by eosinophils and postulated to regulate eosinophil development and migration. We report that Pirb is upregulated in the esophagus after inducible overexpression of IL-13 (CC10-IL13 Tg mice) and is overexpressed by esophageal eosinophils. CC10-IL13Tg/PirB-/- mice displayed increased esophageal eosinophilia and EoE pahtology, including epithelial cell thickening, fibrosis and angiogenesis, compared with CC10-IL13 Tg/PirB+/+ mice. Transcriptome analysis of primary Pirb+/+ and Prib-/- esophageal eosinophils revealed increased expression of transcripts associated with promoting tissue remodeling in Pirb-/- eosinophils including pro-fibrotic genes, genes promoting epithelial-to-mesenchymal transition (EMT) and genes associated with epithelial growth. These data identify PIR-B as a molecular checkpoint in IL-13-induced eosinophil accumulation and activation, which may serve as a novel target for future therapy in EoE. Overall design: 17 samples are analyzed in this experiment. The experiment was designed with 3 replicates for each treatment/genotype/tissue (Dox and no Dox/wildtype and knockout/bone marrow and esophagus), with the exception of the sample wildtype bone marrow no Dox where 1 replicate was dropped due to low hybridization signal. The no Dox and wildtype samples are controls for the treatment and background of the mice.